The specific objective of this proposal is to determine the relative contributions of membrane solid, structural elements (which appear to be a protein "matrix") and the lipid bilayer component to membrane cohesion and resistance to lysis. Membrane "failure" can be separated into two mechanisms: (1) lysis; (2) fragmentation. This proposal is directly related to the lysis mechanisms and contains the following important aspects: (1) determination of membrane free energy, tension, and area changes in uniform dilation; (2) comparison of in-vitro lipid vesicle properties with red cell spherocytes (osmotically preswollen normal cells, ATP depleted cells, and hereditary spherocytosis cells); (3) time statistics and thermodynamic basis of lysis related to surface free energy density and area dilation; (4) temperature dependence of surface properties. Because the lipid bilayer possesses no shear rigidity, the comparison of lipid bilayer contributions to whole membrane structure must be made using the membrane area dilation properties of the mechano-chemical equation of state. Therefore, the basic approach is to experimentally determine the membrane free energy density, isotropic tension, and area dilation by micropipette aspiration of red cell spherocytes and lipid vesicles. Comparison of lipid bilayer systems, lipid-protein complex systems, and intact cell membranes is essential to ascertain structural roles for the components and the determinants of membrane viability. Clinically, the study provides the basis for investigation into the mechano-chemical origins of cell lysis associated with immunological reaction, anemias, exposure to artificial surfaces, and reduced cell life spans in general.